Research Projects

Glucocerebrosidase, a lysosomal enzyme, is crucial for the hydrolysis of glucocerebroside glycolipid metabolism pathways. Decreased or absent Glucocerebrosidase activity results in Gaucher disease (GD), a rare genetic disorder affecting the whole body. Enzyme replacement therapy (ERT) is used to treat GD using recombinant human Glucocerebrosidase rhGCS biotherapeutic. However, all three enzymes are unaffordable, costing several 10s of Lakhs per patient/year and being taken life-long. In India, 150 patients receive ERT, but all are imported and unavailable through private health insurance. This proposal aims to develop affordable biotherapeutic rhGCS, aiming to decrease the cost by 80-90 from the current cost. Cerezyme patents have expired, offering an appropriate avenue. The process involves extensive modification of glycan chains in CHO expressed glucocerebrosidase to convert the protein into the drug substance. Tranalab, an industry partner of ICT Mumbai, has developed a CHO clone expressing rhGCS in a form secreted into CHO growth media. The project aims to increase rhGCS yield by examining different conditions like CHO cell density and production run time, with a target of at least 200 mg/Lt crude yield. Tranalab has also developed E. coli clones expressing the three different deglycosylation enzymes, which will be scaled-up and purified to deglycosylate CHO produced rhGCS.